Nonstructural Nipah Virus C Protein Regulates both the Early Host Proinflammatory Response and Viral Virulence

• DOI: 10.1128/jvi.01203-12
• Publication Date: 2012-07-27T07:52:34Z
• Authors: Cyrille Mathieu; Vanessa Guillaume; Valentina A. Volc...; Christine Pohl; Frederique Jacquot; Ren Yih Looi; Kum Thong Wong; Catherine Legras-...; Viktor E. Volchkov; Joel Lachuer; Branka Horvat
• Keywords: Proinflammatory cytokine

Nipah virus (NiV) is a highly pathogenic, negative-strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. We have analyzed the role of nonstructural NiV C protein in viral immunopathogenesis using recombinant lacking expression (NiVΔC). While wild-type was pathogenic hamster animal model, NiVΔC strongly attenuated. Replication followed by production NiV-specific antibodies and associated with higher recruitment inflammatory cells less intensive histopathological lesions different organs than wild-type-NiV-infected animals. To analyze molecular basis attenuation, we studied early changes gene infected primary endothelial cells, major cellular target infection. The transcriptomic approach revealed striking difference between mutant genes involved immunity, particularly interesting differential patterns proinflammatory cytokines. Compared virus, induced increased interleukin 1 beta (IL-1β), IL-8, CXCL2, CXCL3, CXCL6, CCL20, interferon. Furthermore, stably transfected decreased same panel cytokines, revealing regulation cytokine balance. Together, these results suggest regulates therefore providing signal responsible for coordination leukocyte chemokine-induced immune response controlling lethal outcome